According to the American Diabetes Association, more than 20 million Americans have diabetes, with a total annual economic cost in the year 2002 of $132 billion dollars. Efforts to manage diabetes and its many serious complications focus on control of glucose levels and prevention of the hyperglycemia that characterizes the disease. Our research in this project has found evidence that caffeine, the drug present in many popular beverages, foods, and medications, contributes to the unhealthy hyperglycemia of type 2 diabetes. Specifically, caffeine exaggerates the glucose and insulin increases that follow a meal (postprandial hyperglycemia and hyperinsulinemia) in men and women with type 2 diabetes and raises daytime glucose levels measured during the activities of normal daily life. We propose two new studies to advance our understanding of the clinical importance of these caffeine effects in the management of diabetes. Although we have shown that caffeine acutely disrupts postprandial glucose disposal, we do not yet know that eliminating caffeine from the diet will improve glycemic control in those patients with type 2 diabetes who habitually consume the drug. We will answer this question with a randomized controlled experimental study. A 2-week intensive investigation will test the short-term efficacy of caffeine abstinence for reduction of glucose levels and postprandial responses. Continued follow-up for 3 months will provide preliminary evidence of treatment effectiveness. This study will combine short and long-term biochemical measures of glucose control with ambulatory measures of glucose during the activities of daily life. We will also compare groups of heavy and light consumers to test a [unreadable]dose-response[unreadable] hypothesis, that those who consume more caffeine will receive greater benefit from quitting the drug. Results from this study will demonstrate the potential clinical benefits of eliminating caffeine from the diet that will guide the larger clinical trials to follow. How caffeine impairs glucose metabolism is also unknown Evidence from healthy young men suggests that caffeine[unreadable]s effects may be mediated by epinephrine release. We will test this hypothesis in patients with type 2 diabetes. A controlled laboratory study will test whether pharmacological beta-adrenergic blockade attenuates or eliminates the effects of caffeine on postprandial glucose and insulin. Establishing this plausible physiological mechanism for caffeine[unreadable]s actions will strengthen arguments for a causal link between caffeine and impaired glucose control in type 2 diabetes. Caffeine is the world[unreadable]s most widely used drug, despite evidence that its effects can be detrimental to health. Proposed studies will advance our understanding of the clinical impact of caffeine consumption on glucose management in type 2 diabetes. Results could lead to recommendations about caffeine consumption that could improve clinical outcomes and reduce complications in the millions of patients with this disease.